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Gates Cambridge scholar targets deadly parasite

A Gates Cambridge Scholar and his team have been granted a patent by the US authorities to develop a treatment for toxoplasmosis – a parasite that can kill people with suppressed immune systems.

Bo Shiun Lai and colleagues submitted a patent application around a year and a half ago when Bo Shiun was still doing his undergraduate degree at the Univesity of Chicago and have just been awarded a US patent.

He is continuing his research at the University of Cambridge in the UK, where he is doing a PhD in Pathology.

Toxoplasmosis is a parasite hosted by two billion people worldwide, mostly without any visible symptoms. However, if their immune system is suppressed – for instance if they are newborn or have HIV – it can cause serious problems.

In newborns it can cause ocular impairment or brain defects while brain inflammation caused by toxoplasmosis is a major cause of death in people with HIV.

It is relatively rare among newborns and has been considered a neglected disease, but since 9/11, it has been classified as a bioterror agent by the US National Institute of Allergy and Infectious Diseases (NIAID) which led to increased interest until the financial meltdown.

Toxoplasmosis takes two forms: active and dormant. When it is dormant the parasite wraps itself in a thick layer of lipid which makes it impervious to all drug treatment and impossible to eradicate.

Bo Shiun’s research into toxoplasmosis focuses on two main challenges: how to deliver drugs across the lipid barrier and what specific molecular pathways to inhibit. As toxoplasmosis mainly resides in the eyes and brain, treatment has to cross the ocular membrane or enter the brain.

His work prior to arriving at Cambridge in 2013 was focused on the first challenge, attempting to create a molecule that could have an inhibitory effect on the parasite and deliver medication across multiple membranes.

At Cambridge, he has been targeting the second challenge – how to switch the parasite from dormant to active mode, making it susceptible to existing treatment, or shut off essential pathways, killing the parasite effectively.

He says: “This approach is a breakthrough because it allows us to deliver drugs across numerous layers of obstacles, arrive at the intended target (ideally essential for parasite survival or replication), and abrogate parasite growth. The patent is promising for delivering inhibitory molecules into both active and dormant parasites.”

The researchers found that their original model had a small therapeutic range in which it could be both effective and non toxic. They believe the toxicity originates from the transductive peptides which help deliver the drugs across the lipid barrier to the parasite and have been trying to reduce it.

So far they have expanded the therapeutic range by about four times. Bo Shiun says: “This means we can increase the dosage dramatically without observable toxicity.”

Bo Shiun's work has seen him nominated for the Cozzarelli Prize, a national award for scientific excellence in a particular scientific discipline and three of his articles were accepted for publication in peer review journals before he finished his undergraduate degree.